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The use of enzymes to catalyse reactions is a well established technique used in modern organic chemistry as the use of biological catalysts can install unique and exquisite stereochemistry and regiochemistry into a synthetic route. This project will explore the development of two enzymes that catalyse important bond forming reactions in the synthesis of an Active Pharmaceutical Ingredient and their suitability for use as industrial biocatalysts.

The ImBioED project seeks to deliver improved economics for the production and isolation of amino acids without the need for extensive plant modifications. We intend to achieve this through the integration of biocatalysis and electrodialysis (ED) technologies. Biocatalytic processes are frequentlyimpeded by enzyme inhibition, which severely limits the scope for improving the volume efficiency of such processes. Building on promising results generated from a previous funded Innovate UK feasibility project we intend to utilise ED to remove inhibitory by-products from biotransformation processes, enabling us to achieve significantly improved levels of product accumulation.

The purpose of this feasibility project is to create a deep systems biology level understanding of the stresses placed upon an organism, under a range of (fed-)batch and continuous fermentation conditions required for the large scale and high titre manufacture of biocatalysts, through the use of the complex analytical techniques of metabolomics and proteomics. The project seeks to understand how variation in the genetic constructs and process conditions used to direct protein production can affect the organism and how these effects might be mitigated against, minimised and controlled by further re-design of the genetic components, feed medium and process conditions. The development of robust fermentation processes has economic advantages, through both cycle time reduction and raw material efficiencies and will have clear impact beyond this feasibility study through the reliable and more economic commercial supply of enzymes to Industrial Biotechnology using industries.

The purpose of the EDAM project is to test the feasibility of combining two well established technologies in order to develop an innovative process for the production and isolation of amino acids. Biocatalysis is a well established technology in the chemical and pharmaceutical industries, allowing the conversion of an amino acid precursor into a target amino acid using 1 or 2 enzymes. Electrodialysis membranes have been used for many years in the water purification industry, however wider applications of this technology remain under utilised. We propose to utilise a two enzyme reaction system to facilitate the production of amino acids. Subsequent application of a direct current electric field to the reaction mixture will then lead to electromigration of the charged amino acid species across an ion exchange membrane and product purification.

Chiral amines are important building blocks used in 40% pharmaceutical products, 20% of crop protection compounds and are high value chemical intermediates. Current synthetic methods use wasteful resolution processes. This project will improve manufacturing efficiency by developing catalytic (transfer) hydrogenation methods to make specific types of chiral amines. The project aims to develop and exploit new catalysts, to develop solid supported variants of these, and use them in novel flow reactors. This allows reduced effective loadings of the metal catalysts, efficient metal recovery and switch from batch to continuous processing. The project generates new asymmetric catalysts, opens new market opportunities for flow reactors, and fulfils high demand for chiral amines required by end user companies made using more efficient processes to lower cost, reduce waste, improve quality and availability.

Awaiting Public Summary